Does Every Patient Need Colonoscopy Follow-up for Diverticulitis?

Background: American College of Gastroenterology guidelines recommend colonoscopy as follow-up after an episode of diverticulitis, as there has been some association between diverticulitis and the diagnosis of colon cancer. There is limited data on the yield of this procedure in this setting. Recent studies have suggested that colonoscopy may only be warranted after episodes of complicated diverticulitis involving CT-proven abscess or reactive lymph nodes, which are associated with a higher likelihood of the presence of occult colon cancer. Objective: The primary objective is to retrospectively examine the results of colonoscopy done for follow-up of diverticulitis at our center, specifically looking for newly diagnosed carcinoma of the colon. We will compare the findings between unique sup-groups based on previous screening status and family history. This study may help to develop future guidelines for follow-up of diverticulitis. Method: A search was performed in the electronic medical record for adult patients with colonoscopy performed for indication “diverticulitis” or “abnormal abdominal CT scan” in the past five years. Of 521 charts screened, 136 with CT-diagnosed diverticulitis and sufficient documentation were included in the study. Data regarding demographics, medical history, imaging, colonoscopy findings, and pathology was reviewed. A descriptive analysis was performed and patient sub-groups were compared using Fisher’s exact test. Results: Of 136 patients with diverticulitis, two had adenocarcinoma of the sigmoid colon diagnosed after follow-up colonoscopy (1.5%). Both carcinomas were diagnosed after first episodes of uncomplicated diverticulitis, and neither in this group had previous colonoscopies. Both localized to the same spot as the diverticulitis by CT. One of the carcinomas was found in a patient under 50 years old who had a reported family history of colon cancer. The second carcinoma was diagnosed in a patient over 50 years old, and this patient had no family history. There was also one neuroendocrine tumor of the rectum incidentally found. There was no significant difference between rates of carcinoma diagnosed among subgroups examined (family history vs. no family history, previous screening colonoscopy vs. never screened, uncomplicated vs. complicated diverticulitis, and age over 50 vs. under 50). Conclusion: Based on these findings, we believe colonoscopy should still be pursued as follow-up after any episode of diverticulitis to rule out occult colon cancer. More evidence and a larger sample size will be needed before recommending changes to the current guidelines

Elucidating the Mechanisms of Influenza Virus Recognition by Ncr1

Natural killer (NK) cells are innate cytotoxic lymphocytes that specialize in the defense against viral infection and oncogenic transformation. Their action is tightly regulated by signals derived from inhibitory and activating receptors; the later include proteins such as the Natural Cytotoxicity Receptors (NCRs: NKp46, NKp44 and NKp30). Among the NCRs, NKp46 is the only receptor that has a mouse orthologue named Ncr1. NKp46/Ncr1 is also a unique marker expressed on NK and on Lymphoid tissue inducer (LTI) cells and it was implicated in the control of various viral infections, cancer and diabetes. We have previously shown that human NKp46 recognizes viral hemagglutinin (HA) in a sialic acid-dependent manner and that the O-glycosylation is essential for the NKp46 binding to viral HA. Here we studied the molecular interactions between Ncr1 and influenza viruses. We show that Ncr1 recognizes influenza virus in a sialic acid dependent manner and that N-glycosylation is important for this binding. Surprisingly we demonstrate that none of the predicted N-glycosilated residues of Ncr1 are essential for its binding to influenza virus and we thus conclude that other, yet unidentified N-glycosilated residues are responsible for its recognition. We have demonstrated that N glycosylation play little role in the recognition of mouse tumor cell lines and also showed the in-vivo importance of Ncr1 in the control of influenza virus infection by infecting C57BL/6 and BALB/c mice knockout for Ncr1 with influenza

In hospital physiotherapy treatment for Covid-19 patients – Management and clinical practice

World Health Organization has declared corona virus disease (COVID 19) a global pandemic and public health emergency, following the outbreak in&nbsp; Wuhan, China in December 2019. Fever, dry cough and fatigue are the main manifestations, but the main concern is cases that deteriorated to severe pneumonia and ARDS. The outbreak of COVID- 19 in Israel, in March 2020 caused major changes in the routine work in hospitals. Hasharon hospital, a small community hospital in Petah Tikvah was converted to corona patients admissions only. In accordance with this new reality the physiotherapy service prepared itself to provide treatments tailored to the clinical needs of the Covid 19 patients and the quarantine conditions of these patients hospitalization. During a period of 2 month, we built a unique protocol adjusted to isolated patients and staff, including telemedicine and hands on treatment. </p

HSV1 MicroRNA Modulation of GPI Anchoring and Downstream Immune Evasion

Herpes simplex virus 1 (HSV1) is a ubiquitous human pathogen that utilizes variable mechanisms to evade immune surveillance. The glycosylphosphatidylinositol (GPI) anchoring pathway is a multistep process in which a myriad of different proteins are covalently attached to a GPI moiety to be presented on the cell surface. Among the different GPI-anchored proteins there are many with immunological importance. We present evidence that the HSV1-encoded miR H8 directly targets PIGT, a member of the protein complex that covalently attaches proteins to GPI in the final step of GPI anchoring. This results in a membrane down-modulation of several different immune-related, GPI-anchored proteins, including ligands for natural killer-activating receptors and the prominent viral restriction factor tetherin. Thus, we suggest that by utilizing just one of dozens of miRNAs encoded by HSV1, the virus can counteract the host immune response at several key points

Mouse TIGIT

The activity of natural killer (NK) cells is controlled by a balance of signals derived from inhibitory and activating receptors. TIGIT is a novel inhibitory receptor, recently shown in humans to interact with two ligands: PVR and Nectin2 and to inhibit human NK-cell cytotoxicity. Whether mouse TIGIT (mTIGIT) inhibits mouse NK-cell cytotoxicity is unknown. Here we show that mTIGIT is expressed by mouse NK cells and interacts with mouse PVR (mPVR). Using mouse and human Ig fusion proteins we show that while the human TIGIT (hTIGIT) cross-reacts with mPVR, the binding of mTIGIT is restricted to mPVR. We further demonstrate using surface plasmon resonance (SPR) and staining with Ig fusion proteins that mTIGIT binds to mPVR with higher affinity than the co-stimulatory PVR-binding receptor mDNAM1. Functionally, we show that triggering of mTIGIT leads to the inhibition of NK-cell cytotoxicity, that IFN-γ secretion is enhanced when mTIGIT is blocked and that the TIGIT-mediated inhibition is dominant over the signals delivered by the PVR-binding co-stimulatory receptors. Additionally, we identify the inhibitory motif responsible for mTIGIT inhibition. In conclusion we show that TIGIT is a powerful inhibitory receptor for mouse NK cells

Mouse TIGIT inhibits NK-cell cytotoxicity upon interaction with PVR

The activity of natural killer (NK) cells is controlled by a balance of signals derived from inhibitory and activating receptors. TIGIT is a novel inhibitory receptor, recently shown in humans to interact with two ligands: PVR and Nectin2 and to inhibit human NK‐cell cytotoxicity. Whether mouse TIGIT (mTIGIT) inhibits mouse NK‐cell cytotoxicity is unknown. Here we show that mTIGIT is expressed by mouse NK cells and interacts with mouse PVR. Using mouse and human Ig fusion proteins we show that while the human TIGIT (hTIGIT) cross‐reacts with mouse PVR (mPVR), the binding of mTIGIT is restricted to mPVR. We further demonstrate using surface plasmon resonance (SPR) and staining with Ig fusion proteins that mTIGIT binds to mPVR with higher affinity than the co‐stimulatory PVR‐binding receptor mouse DNAM1 (mDNAM1). Functionally, we show that triggering of mTIGIT leads to the inhibition of NK‐cell cytotoxicity, that IFN‐γ secretion is enhanced when mTIGIT is blocked and that the TIGIT‐mediated inhibition is dominant over the signals delivered by the PVR‐binding co‐stimulatory receptors. Additionally, we identify the inhibitory motif responsible for mTIGIT inhibition. In conclusion, we show that TIGIT is a powerful inhibitory receptor for mouse NK cells

HCMV vCXCL1 Binds Several Chemokine Receptors and Preferentially Attracts Neutrophils over NK Cells by Interacting with CXCR2

Summary: HCMV is a highly sophisticated virus that has developed various mechanisms for immune evasion and viral dissemination throughout the body (partially mediated by neutrophils). NK cells play an important role in elimination of HCMV-infected cells. Both neutrophils and NK cells utilize similar sets of chemokine receptors to traffic, to and from, various organs. However, the mechanisms by which HCMV attracts neutrophils and not NK cells are largely unknown. Here, we show a unique viral protein, vCXCL1, which targets three chemokine receptors: CXCR1 and CXCR2 expressed on neutrophils and CXCR1 and CX3CR1 expressed on NK cells. Although vCXCL1 attracted both cell types, neutrophils migrated faster and more efficiently than NK cells through the binding of CXCR2. Therefore, we propose that HCMV has developed vCXCL1 to orchestrate its rapid systemic dissemination through preferential attraction of neutrophils and uses alternative mechanisms to counteract the later attraction of NK cells. : Viral CXCL1 (vCXCL1) is a chemokine produced following infection with human cytomegalovirus. Yamin et al. show here that vCXCL1 binds to three chemokine receptors: CXCR1, CXCR2, and CX3CR1 and that neutrophils migrate faster and more efficiently than NK cells toward vCXCL1 through binding to CXCR2 expressed by neutrophils only